Breast cancer remains the second leading cause of cancer death of women in the United States. Preventive measures with minimal adverse effects are needed to reduce the incidence and progression of breast cancer. The long-term research goal of the principal investigator, Dr. Yee, is to investigate the molecular mechanisms of breast cancer progression and ultimately develop new interventions for breast cancer prevention and eradication. Dr. Yee is requesting funds to develop her skills in breast cancer prevention and control, an effort that will complement her training as a surgeon specializing in breast cancer and allow her to conduct the future translational research vital to reducing breast cancer risk. Her training in preventive oncology will encompass mentorship by select faculty of The Ohio State University, Comprehensive Cancer Center and James Cancer Hospital and Solove Research Institute, combining didactic course work and a cancer prevention research project. The plan integrates molecular genetics, nutritional sciences, and clinical breast cancer research. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that stimulate transcriptional activity in response to ligands such as fatty acids and prostaglandins. The PPARgamma subtype regulates cell differentiation and proliferation in normal and malignant tissues. Cell culture and animal models will be used to evaluate fatty acid effects on PPARgamma activation in breast cancer. Human breast tumors and surrounding fat and epithelial tissue will also be assessed for patterns of expression of PPARs and other factors affecting PPAR activation. This work will serve to generate data to support a prospective clinical study of the effects of dietary fat and PPARgamma on breast cancer progression. Combined with a didactic course of study in a stimulating scientific and clinical environment, this project will give Dr. Yee the training required to become an independent clinician scientist in the field of preventive oncology.